title: Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells.
abstract: 9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 μM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity.
authors.affiliation: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. nhatae@hoku-iryo-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hatae
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Okujima
authors.forename: Minoru
authors.initials: M
authors.lastname: Ishikura
authors.forename: Takumi
authors.initials: T
authors.lastname: Abe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hibino
authors.forename: Tominari
authors.initials: T
authors.lastname: Choshi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Okada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamada
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Uno
authors.forename: Eiko
authors.initials: E
authors.lastname: Toyota
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010616:Phenanthrenes; C005399:9,10-phenanthrenequinone
keywords: 9,10-Phenanthrenequinone; Antitumor activity; Apoptosis; Diesel exhaust particulates; Orthoquinone